This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The first crucial step of mammalian embryo development after fertilization is to generate two types of cell populations, known as trophectoderm (TE) and inner cell mass (ICM). TE engages in the attachment with the mother's uterus for implantation and placenta formation, whereas ICM serves as embryonic stem cells to produce all the tissues in the fetus. Thus, both TE and ICM need to be created correctly during embryo development to achieve successful pregnancy and the growth of a healthy fetus. Genetic and environmental factors are likely to affect these processes, which may lead to various reproductive problems, such as infertility and pregnancy-related malignant cancers like choriocarcinoma and teratocarcinoma. However, how TE and ICM are created during embryo development is still not well-understood. The purpose of the project is to elucidate the genetic and molecular mechanisms that generate these two cell populations. The studies will be conducted mainly with mouse embryos as an experimental model, but the obtained information will also be assessed in human embryos. Specifically, we will test the roles of cell polarity regulators, known as Par genes, in the formation of TE and ICM. The hypothesis is that Par genes first establish polarized structures within each embryonic cell, which then serves as the spatial foundation to generate two different types of cell populations within an embryo. The study will reveal the function of Par genes in the formation of TE and ICM, and will also add to our understanding of human health issues on reproductive problems.